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https://www.readbyqxmd.com/read/29686743/antinociceptive-activity-of-methanolic-extract-of-clinacanthus-nutans-leaves-possible-mechanisms-of-action-involved
#1
Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Rushduddin Al Jufri Roosli, Mohd Hijaz Mohd Sani, Maizatul Hasyima Omar, Siti Farah Mohd Tohid, Fezah Othman, Siew Mooi Ching, Arifah Abdul Kadir
Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes ( β -funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α 2 -noradrenergic (yohimbine), β -adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride)...
2018: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/29686613/essential-control-of-the-function-of-the-striatopallidal-neuron-by-pre-coupled-complexes-of-adenosine-a-2a-dopamine-d-2-receptor-heterotetramers-and-adenylyl-cyclase
#2
Sergi Ferré, Jordi Bonaventura, Wendy Zhu, Candice Hatcher-Solis, Jaume Taura, César Quiroz, Ning-Sheng Cai, Estefanía Moreno, Verónica Casadó-Anguera, Alexxai V Kravitz, Kimberly R Thompson, Dardo G Tomasi, Gemma Navarro, Arnau Cordomí, Leonardo Pardo, Carme Lluís, Carmen W Dessauer, Nora D Volkow, Vicent Casadó, Francisco Ciruela, Diomedes E Logothetis, Daniel Zwilling
The central adenosine system and adenosine receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by the strategic co-localization of different adenosine and dopamine receptor subtypes in the two populations of striatal efferent neurons, striatonigral and striatopallidal, that give rise to the direct and indirect striatal efferent pathways, respectively. With optogenetic techniques it has been possible to dissect a differential role of the direct and indirect pathways in mediating "Go" responses upon exposure to reward-related stimuli and "NoGo" responses upon exposure to non-rewarded or aversive-related stimuli, respectively, which depends on their different connecting output structures and their differential expression of dopamine and adenosine receptor subtypes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29681853/caffeine-promotes-conversion-of-palmitic-acid-to-palmitoleic-acid-by-inducing-expression-of-fat-5-in-caenorhabditis-elegans-and-scd1-in-mice
#3
Xiaocui Du, Qin Huang, Yun Guan, Ming Lv, Xiaofang He, Chongye Fang, Xuanjun Wang, Jun Sheng
The synthesis and metabolism of fatty acids in an organism is related to many biological processes and is involved in several diseases. The effects of caffeine on fatty acid synthesis and fat storage in Caenorhabditis elegans and mice were studied. After 6 h of food deprivation, adult C. elegans were treated with 0.1 mg/mL caffeine for 24 h. Quantitative reverse-transcription polymerase chain reaction showed that, among all the genes involved in fat accumulation, the mRNA expression of fat-5 in caffeine-treated C...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29655598/individual-differences-in-the-energizing-effects-of-caffeine-on-effort-based-decision-making-tests-in-rats
#4
Noemí SanMiguel, Marta Pardo, Carla Carratalá-Ros, Laura López-Cruz, John D Salamone, Mercè Correa
Motivated behavior is characterized by activation and high work output. Nucleus accumbens (Nacb) modulates behavioral activation and effort-based decision-making. Caffeine is widely consumed because of its energizing properties. This methylxanthine is a non-selective adenosine A1 /A2A receptor antagonist. Adenosine receptors are highly concentrated in Nacb. Adenosine agonists injected into Nacb, shift preference towards low effort alternatives. The present studies characterized effort-related effects of caffeine in a concurrent progressive ratio (PROG)/free reinforcer choice procedure that requires high levels of work output, and generates great variability among different animals...
April 12, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29614315/a-novel-pharmacological-activity-of-caffeine-in-the-cholinergic-system
#5
Camila Fabiani, Ana Paula Murray, Jeremías Corradi, Silvia Susana Antollini
Cholinergic deficit is regarded as an important factor responsible for Alzheimer's disease (AD) symptoms. Acetylcholinesterase (AChE) and nicotinic receptor (AChR) are two molecular targets for the treatment of this disease. We found here that methanolic extracts of Camellia sinensis exhibited anticholinesterase activity and induced AChR conformational changes. From bioguided fractionation we confirmed that caffeine was the active compound exerting such effects. It is well-known that caffeine acts as an inhibitor of AChE and here we explored the effect of caffeine on the AChR by combining single channel recordings and fluorescent measurements...
March 31, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29604187/investigating-the-possible-mechanisms-involved-in-adenosine-preconditioning-induced-cardioprotection-in-rats
#6
Lovedeep Singh, Jasleen Kaur Virdi, L N Maslov, Nirmal Singh, Amteshwar Singh Jaggi
BACKGROUND: Adenosine is a breakdown product of adenosine triphosphate and plays an important role in pharmacological preconditioning. The cardioprotective effects of adenosine preconditioning are well established. However, the possible mechanisms need to be explored. AIM: The present study was aimed to investigate the possible mechanisms involved in adenosine preconditioning-induced cardioprotection in rats. METHODS: Rat heart was isolated and perfused on Langendorff apparatus...
March 31, 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29590460/coffee-consumption-and-reduced-risk-of-developing-type-2-diabetes-a-systematic-review-with-meta-analysis
#7
Mattias Carlström, Susanna C Larsson
Context: Type 2 diabetes (T2D) is a major health problem worldwide that is associated with increased morbidity and mortality. There is increased interest in the value of different nutrition-based strategies for preventing the development of T2D. Objective: This review aims to cover current knowledge regarding the effects of coffee consumption on development of T2D or modulation of adverse complications. A meta-analysis on coffee consumption and the risk of T2D was conducted...
March 26, 2018: Nutrition Reviews
https://www.readbyqxmd.com/read/29569723/cytochrome-p450-3a-induction-predicts-p-glycoprotein-induction-1-establishing-induction-relationships-using-ascending-dose-rifampin
#8
Justin D Lutz, Brian J Kirby, Lu Wang, Qinghua Song, John Ling, Benedetta Massetto, Angela Worth, Brian P Kearney, Anita Mathias
Drug transporter and cytochrome P450 expression is regulated by shared nuclear receptors and hence, an inducer should induce both, though magnitude may differ. The objective of this study was to establish relative induction relationships between CYP3A and drug transporters (P-gp, OATP and BCRP) or other P450s (CYP2C9 and CYP1A2) using ascending doses of the prototypical PXR agonist, rifampin, to elicit weak, moderate and strong PXR agonism. Healthy subjects received dabigatran etexilate, pravastatin, rosuvastatin and a midazolam/tolbutamide/caffeine cocktail before and after rifampin 2, 10, 75, or 600 mg qd...
March 23, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29568380/adenosine-a-2a-receptor-ligand-recognition-and-signaling-is-blocked-by-a-2b-receptors
#9
Sonja Hinz, Gemma Navarro, Dasiel Borroto-Escuela, Benjamin F Seibt, York-Christoph Ammon, Elisabetta de Filippo, Azeem Danish, Svenja K Lacher, Barbora Červinková, Muhammad Rafehi, Kjell Fuxe, Anke C Schiedel, Rafael Franco, Christa E Müller
The adenosine receptor (AR) subtypes A2A and A2B are rhodopsin-like Gs protein-coupled receptors whose expression is highly regulated under pathological, e.g. hypoxic, ischemic and inflammatory conditions. Both receptors play important roles in inflammatory and neurodegenerative diseases, are blocked by caffeine, and have now become major drug targets in immuno-oncology. By Förster resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), bimolecular fluorescence complementation (BiFC) and proximity ligation assays (PLA) we demonstrated A2A -A2B AR heteromeric complex formation...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29563862/caffeine-protects-dopaminergic-neurons-from-dopamine-induced-neurodegeneration-via-synergistic-adenosine-dopamine-d2-like-receptor-interactions-in-transgenic-caenorhabditis-elegans
#10
Rafael V M Manalo, Paul M B Medina
Previous studies have suggested that caffeine reduces the risk of L-DOPA-induced dyskinesia. However, caffeine is also known to promote dopamine signaling, which seemingly contradicts this observed effect. To this end, the study aimed to clarify the mechanism of caffeine neuroprotection in vivo when excess dopamine is present. Transgenic Caenorhabditis elegans (UA57) overproducing dopamine was exposed to caffeine for 7 days and monitored by observing GFP-tagged dopaminergic (DA) neurons via fluorescence microscopy...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29557061/differential-behavioral-and-biochemical-responses-to-caffeine-in-male-and-female-rats-from-a-validated-model-of-attention-deficit-and-hyperactivity-disorder
#11
Fernanda Nunes, Daniela Pochmann, Amanda Staldoni Almeida, Daniela Melo Marques, Lisiane de Oliveira Porciúncula
Epidemiological studies suggest sex differences in attention deficit and hyperactivity disorder (ADHD) symptomatology. The potential benefits of caffeine have been reported in the management of ADHD, but its effects were not properly addressed with respect to sex differences. The present study examined the effects of caffeine (0.3 g/L) administered since childhood in the behavior and brain-derived neurotrophic factor (BDNF) and its related proteins in both sexes of a rat model of ADHD (spontaneously hypertensive rats-SHR)...
March 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29556329/overcoming-chemoresistance-in-pancreatic-cancer-cells-role-of-the-bitter-taste-receptor-t2r10
#12
Louisa Stern, Nathalia Giese, Thilo Hackert, Oliver Strobel, Peter Schirmacher, Klaus Felix, Matthias M Gaida
Bitter taste receptors (T2Rs) are G-protein coupled transmembrane proteins initially identified in the gustatory system as sensors for the taste of bitter. Recent evidence on expression of these receptors outside gustatory tissues suggested alternative functions, and there is growing interest of their potential role in cancer biology. In this study, we report for the first time, expression and functionality of the bitter receptor family member T2R10 in both human pancreatic ductal adenocarcinoma (PDAC) tissue and PDAC derived cell lines...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29549309/coupling-of-sk-channels-l-type-ca-2-channels-and-ryanodine-receptors-in-cardiomyocytes
#13
Xiao-Dong Zhang, Zana A Coulibaly, Wei Chun Chen, Hannah A Ledford, Jeong Han Lee, Padmini Sirish, Gu Dai, Zhong Jian, Frank Chuang, Ingrid Brust-Mascher, Ebenezer N Yamoah, Ye Chen-Izu, Leighton T Izu, Nipavan Chiamvimonvat
Small-conductance Ca2+ -activated K+ (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca2+ microdomains necessary for SK channel activation. SK currents coupled with Ca2+ influx via L-type Ca2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca2+ store, suggesting that LTCCs provide the immediate Ca2+ microdomain for the activation of SK channels in cardiomyocytes...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29537866/negative-regulation-of-cellular-ca-2-mobilization-by-ryanodine-receptor-type-3-in-mouse-mesenteric-artery-smooth-muscle
#14
Katsuhito Matsuki, Daiki Kato, Masashi Takemoto, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroshi Takeshima, Yuji Imaizumi
Physiological functions of type 3 ryanodine receptors (RyR3) in smooth muscle (SM) tissues are not well understood, in spite of their wide expression. However, the short isoform of RyR3 is known to be a dominant negative variant (DN-RyR3), which may negatively regulate functions of both RyR2 and full length (FL)-RyR3 by forming hetero-tetramers. Here, functional roles of RyR3 in the regulation of Ca2+ signaling in mesenteric artery SM cells (MASMCs) were examined using RyR3 homozygous knockout mice (RyR3-/- )...
March 14, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29535001/3-4-chlorophenylselanyl-1-methyl-1h-indole-a-new-selenium-compound-elicits-an-antinociceptive-and-anti-inflammatory-effect-in-mice
#15
Paloma T Birmann, Fernanda S S Sousa, Daniela H de Oliveira, Micaela Domingues, Beatriz M Vieira, Eder J Lenardão, Lucielli Savegnago
Several pathologies, such as pain and inflammation, are modulated by different pathways, making it necessary to develop drugs capable of modulating different pathways. Based on that, we investigated the antinociceptive and anti-inflammatory effect of 3-(4-chlorophenylselanyl)-1-methyl-1H-indole (CMI), as well as the systems involved in these actions. This study evaluated the antinociceptive and anti-inflammatory effects of CMI [0.0001-10mg/kg administered intragastrically (i.g.)] in the formalin, glutamate, hot plate, ear edema induced by croton oil and paw edema induced by formalin tests...
March 10, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29518399/nicotine-and-caffeine-alter-the-effects-of-the-lps-primed-mesenchymal-stem-cells-on-the-co-cultured-neutrophils
#16
Ardeshir Abbasi, Nasim Rahmani Kukia, Seyyed Meysam Abtahi Froushani, Seyed Mahmoud Hashemi
PURPOSE: Mesenchymal stem cells (MSCs) express some of the nicotinic receptor subunits and adenosine receptors. The communication between tissue MSCs with neutrophils has been shown in previous studies. The aim of the present study is to determine the role of nicotine or caffeine on MSCs and its effects on neutrophils. METHODS: After the isolation, MSCs were pulsed with LPS (10 ng/ml) for 1 h. Then, MSCs were incubated with different concentrations of caffeine (0...
April 15, 2018: Life Sciences
https://www.readbyqxmd.com/read/29516413/interplay-between-adenosine-receptor-antagonist-and-cyclooxygenase-inhibitor-in-haloperidol-induced-extrapyramidal-effects-in-mice
#17
Devinder Arora, Jayesh Mudgal, Madhavan Nampoothiri, Sanchari Basu Mallik, Manas Kinra, Susan Hall, Shailendra Anoopkumar-Dukie, Gary D Grant, Chamallamudi Mallikarjuna Rao
Antipsychotic drugs are the mainstay of psychotic disorders. The 'typical' antipsychotic agents are commonly employed for the positive symptoms of schizophrenia, though at an expense of extrapyramidal side effects (EPS). In the present study, we employed haloperidol (HP)-induced catalepsy model in mice to evaluate the role of adenosine receptor antagonist and cyclooxygenase (COX) enzyme inhibitor in the amelioration of EPS. HP produced a full blown catalepsy, akinesia and a significant impairment in locomotion and antioxidant status...
March 7, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29516286/npp1-is-responsible-for-potent-extracellular-atp-hydrolysis-as-ntpdase1-in-primary-cultured-murine-microglia
#18
Hye Min Lim, Woon Heo, Jung Woo Han, Min Goo Lee, Joo Young Kim
The movement of microglia is regulated mainly by P1 and P2 purinergic receptors, which are activated by various nucleotides and their metabolites. Recently, such purinergic signalling has been spotlighted because of potential roles in the pathophysiologies of neurodegenerative and neuropsychiatric disorders. To understand the characteristics of microglia in relation of P1 and P2 signalling, we investigated the ectoenzymes expressed in microglia. At first, we profiled the expression of all known ectoenzymes in cultured microglia...
March 7, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29514871/interindividual-differences-in-caffeine-metabolism-and-factors-driving-caffeine-consumption
#19
REVIEW
Astrid Nehlig
Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for decades that the metabolism, clearance, and pharmacokinetics of caffeine is affected by many factors such as age, sex and hormones, liver disease, obesity, smoking, and diet. Caffeine also interacts with many medications. All these factors will be reviewed in the present document and discussed in light of the most recent data concerning the genetic variability affecting caffeine levels and effects at the pharmacokinetic and pharmacodynamic levels that both critically drive the level of caffeine consumption...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29499247/multidimensional-chemobehavior-analysis-of-flavonoids-and-neuroactive-compounds-in-zebrafish
#20
Sean M Bugel, Robert L Tanguay
The comparative analysis of complex behavioral phenotypes is valuable as a reductionist tool for both drug discovery and defining chemical bioactivity. Flavonoids are a diverse class of chemicals that elicit robust neuroactive and hormonal actions, though bioactivity information is limited for many, particularly for neurobehavioral endpoints. Here, we used a zebrafish larval chemomotor response (LCR) bioassay to comparatively evaluate a suite of 24 flavonoids, and in addition a panel of 30 model neuroactive compounds representing diverse modes of action (e...
February 27, 2018: Toxicology and Applied Pharmacology
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